crossing96/oncoscreening huggingface dataset:
CircNR3C1 inhibits proliferation of bladder cancer cells by sponging miR-27a-3p and downregulating cyclin D1 expression.	"Accumulating evidences suggest that circular RNAs play vital roles in human cancers. Previously, we found that circHIPK3 suppressed invasion of bladder cancer cells via sponging miR-558 and downregulating heparanase expression. In this study, we discovered that a circular RNA derived from NR3C1 (circNR3C1) was downregulated in bladder cancer tissues and cell lines according to RNA-Seq data and qRT-PCR analysis. Functionally, we found that overexpression of circNR3C1 could significantly inhibit cell cycle progression and proliferation of bladder cancer cells in vitro, as well as suppress tumor growth in vivo. Mechanistically, we demonstrated that circNR3C1 possessed four targeting sites of miR-27a-3p and could effectively sponge miR-27a-3p to suppress the expression of cyclin D1. Furthermore, we revealed that miR-27a-3p functioned as an oncogene through interacting with 5'UTR of cyclin D1 to enhance its expression, which led to promote cell cycle progression and proliferation in bladder cancer cells. Conclusively, our findings further confirm the hypothesis that circRNAs function as ""microRNA sponges"", and our data suggest that circNR3C1 and miR-27a-3p would be potential therapeutic targets for bladder cancer treatment."	bladder
Contemporary oncologic outcomes of second induction course BCG in patients with nonmuscle invasive bladder cancer.	PURPOSE: According to the 2016 American Urological Association (AUA) guidelines for nonmuscle invasive bladder cancer (NMIBC), clinicians should offer a 2nd intravesical induction course of Bacillus Calmette-Guérin (BCG) to patients with persistent or recurrent Ta or CIS disease after a 1st BCG induction course. However, evidence for a 2nd course is limited, and some patients forego a 2nd induction of BCG in favor of a clinical trial or alternate intravesical therapy. We sought to investigate contemporary oncologic outcomes of a 2nd induction course of BCG in a multi-institutional cohort. MATERIALS AND METHODS: Three hundred fifty-three patients who received full induction BCG for NMIBC since 2001 at 2 institutions were identified. Patients were categorized as receiving primary 6-week induction therapy or subsequent 2nd 6-week induction therapy for patients who recurred or persisted. The baseline differences in demographic and tumor characteristics were compared between the 2 groups, and Kaplan-Meier curves were constructed to assess high-grade recurrence free survival (HgRFS) among both groups. Univariable logistic regression was used to determine factors associated with recurrence after 2nd course BCG RESULTS: A total of 353 patients received 1st induction BCG (BCG1) and 116 patients received a 2nd induction course (BCG2). Maintenance therapy was given to 117 (33.1%) patients after BCG1 and 43 (37.1%) patients after BCG2. Both cohorts were similar in demographics including age, sex, and race. Pathologic stage before treatment differed as BCG1 patients were more likely to have T1 (40.8% vs. 25%) and less likely to have CIS (13.9% vs. 33.6%) (P < 0.001). Complete response (CR) 3 months after BCG1 was observed in 276 patients (78.2%) and 104 patients (89.7%) after BCG2. Responses remained durable, with 36-month CR of 54.7% in BCG1 and 65.6% in BCG2. Progression to MIBC was identified in 1.4% of BCG1 patients vs. 3.4% in BCG2 patients (P = 0.17). Pathologic stage before BCG2 does not predict progression to MIBC (P = 0.21) after BCG2. The time interval between the 1st and 2nd induction of BCG was not significantly associated with response to 2nd induction BCG (P = 0.47). Maintenance therapy after BCG2 was associated with decreased recurrence after 2nd induction course of BCG. CONCLUSION: A 2nd course of BCG is efficacious with a durable HgRFS, validating the recommendations of the 2016 AUA guidelines.	bladder
Indoleamine-2,3-dioxygenase-1 expression predicts poorer survival and up-regulates ZEB2 expression in human early stage bladder cancer.	PURPOSES: Indoleamine-2,3-dioxygenase-1 (IDO1) is a key enzyme of tryptophan metabolism which regulates T cell function in immune cells and little is known about the role of IDO1 expression in bladder cancer cells. The study is aimed to evaluate the clinical relevance of IDO1 expression in human bladder urothelial carcinoma (UC). MATERIALS AND METHODS: One hundred and sixty paraffin-embedded UC tissues (130 bladder, 30 upper urinary tract) and 47 adjacent normal tissues were retrieved for IDO1 immunostaining. Urine samples from UC and non-UC patients were collected before surgery for measuring the concentration of tryptophan and its metabolites. Clinicopathological correlates of IDO1 expression and the prognostic values in human bladder cancer were explored. External validation was performed with 4 published bladder cancer datasets, as well as in vitro studies. RESULTS: As compared with normal adjacent tissues, UC exhibited a higher frequency of IDO1 expression (chi-square, P = 0.0005). IDO1 expression is an independent poor prognostic factor for disease progression [hazard ratio and 95% confidence interval, 3.80 (1.46-9.86), P = 0.006], which is associated with decreased number of intratumoral infiltrating CD8+ lymphocyte (unpaired t test, P = 0.026). External validation showed that patients with higher IDO1 expression exhibit decreased disease-specific survival than those with lower IDO1 expression. Furthermore, IDO1 expression correlated positively with the expression of several EMT markers, including ZEB2, fibronectin and vimentin. The in vitro T24 cell subline demonstrated that IDO1 expression can up-regulate ZEB2 expression probably through miR-200c signaling. CONCLUSION: IDO1 expression predicts poorer survival and up-regulates ZEB2 expression in human bladder cancer.	bladder
Biological molecular layer classification of muscle-invasive bladder cancer opens new treatment opportunities.	BACKGROUND: Muscle-invasive bladder tumors are associated with a high risk of relapse and metastasis even after neoadjuvant chemotherapy and radical cystectomy. Therefore, further therapeutic options are needed and molecular characterization of the disease may help to identify new targets. The aim of this study was to characterize muscle-invasive bladder tumors at the molecular level using computational analyses. METHODS: The TCGA cohort of muscle-invasive bladder cancer patients was used to describe these tumors. Probabilistic graphical models, layer analyses based on sparse k-means coupled with Consensus Cluster, and Flux Balance Analysis were applied to characterize muscle-invasive bladder tumors at a functional level. RESULTS: Luminal and Basal groups were identified, and an immune molecular layer with independent value was also described. Luminal tumors showed decreased activity in the nodes of epidermis development and extracellular matrix, and increased activity in the node of steroid metabolism leading to a higher expression of the androgen receptor. This fact points to the androgen receptor as a therapeutic target in this group. Basal tumors were highly proliferative according to Flux Balance Analysis, which makes these tumors good candidates for neoadjuvant chemotherapy. The Immune-high group showed a higher degree of expression of immune biomarkers, suggesting that this group may benefit from immune therapy. CONCLUSIONS: Our approach, based on layer analyses, established a Luminal group candidate for therapy with androgen receptor inhibitors, a proliferative Basal group which seems to be a good candidate for chemotherapy, and an immune-high group candidate for immunotherapy.	bladder
[Investigation of Clinical Outcome and Prognosis of 2nd TUR-Bt for T1 High Grade Bladder Cancer].	Second transurethral resection of bladder tumor (TUR-Bt) is a standard treatment for high grade T1 initial, non-muscle invasive bladder cancer. In our hospital from October 2008 to April 2017, 2nd TUR-Bt was performed in 51 cases of initial T1 bladder cancer. The risk factors of residual tumors on 2nd TUR-Bt and the clinical outcome were examined retrospectively. Twenty two of the 51 cases (43.1%) had residual tumors on 2nd TUR-Bt, and upstaging was not admitted. To determine the risk factor for residual tumors in 2nd TUR-Bt, we examined gender, tumor morphology (papillary/non-papillary, pedunculated/ nonpedunculated), number of tumors (single/frequent), and tumor size (≧20 mm/＜20 mm), but none of these were significant risk factors for tumor residue. The recurrence free survival (RFS) of the 51 cases was 86.0% after 1 year, and 77.0% after 3 years. There tended to be a higher RFS in the pedunculated tumor group, pT0 group on 2nd TUR-Bt, intravesical BCG therapy group, but no statistically significant difference was observed. The progression free survival (PFS) was 90.6% after 3 years, and 87.3% after 5 years. These values were similar to those reported previously.	bladder
Recurrent Ta Low-grade Non-muscle-invasive Bladder Cancer: What Are the Options?	"Recurrent low-grade Ta tumours, classified as intermediate-risk non-muscle-invasive bladder cancer (NMIBC), have a high risk of recurrence but a low risk of progression. This case presents a 60-yr-old female with intermediate-risk NMIBC who has been treated with sequential courses of mitomycin C followed by bacillus Calmette-Guérin (BCG). She continued to develop multiple episodes of recurrence. The discussion addresses whether the best course is repeat transurethral resection of the bladder with continued monitoring, more of the same intravesical treatments, new methods of applying these treatments, or novel treatments that might involve enrolling the patient in a clinical trial. The biggest unmet need in the field comes from the lack of a molecular marker that could help select patients for aggressive strategies. PATIENT SUMMARY: Following treatment of intermediate-risk non-muscle-invasive bladder cancer with a fairly standard course of intravesical drug therapy, the patient, a relatively young woman, continued to develop recurrences of the bladder cancer. The authors discuss whether the best next course is ""more of the same"", device-assisted application of these treatments, or perhaps one of the new, still investigatory treatment approaches. Radical surgery (removal of the bladder) should not be necessary unless the recurrences show signs of disease progression."	bladder
Prognostic Impact of Canonical TGF-β Signaling in Urothelial Bladder Cancer.	Background and objectives: Dysregulation of TGF-β signaling plays multiple roles in cancer development and progression. In the canonical TGF-β pathway, TGF-β regulates the expression of hundreds of target genes via interaction with Smads, signal transducers and transcriptional modulators. We evaluated the association of TGF-β1, Smad2, and Smad4, the key components of canonical TGFβ pathway, with clinicopathologic characteristics of urothelial bladder cancer, and assessed their prognostic value in prediction of patients' outcome. Materials and Methods: Immunohistochemical analysis of TGF-β1, Smad2, and Smad4 expression was performed on 404 urothelial bladder cancer samples, incorporated in tissue microarrays. Expression status was correlated with clinicopathological and follow-up data. The median follow-up was 61 months. Results: High expression of TGF-β1, Smad2, and Smad4 was detected in 68.1%, 31.7% and 45.2% of the tumors, respectively. TGF-β1 overexpression was significantly associated with high tumor grade, and advanced pathologic stage (p < 0.001, respectively). Conversely, high Smad2 and Smad4 expression was linked to low tumor grade (p = 0,003, p = 0.048, respectively), and low tumor stage (p < 0.001, p = 0.003, respectively). Smad2 showed an inverse correlation with variant morphology and divergent differentiation of urothelial tumors (p = 0.014). High TGF-β1 correlated directly, while Smad2 and Smad4 correlated inversely to cancer-specific death (p = 0.043, p = 0.003, and p = 0.022, respectively). There was a strong relationship between Smad2 and Smad4 expression (p < 0.001). Survival analyses showed that high Smad2 and Smad4 expression was associated with longer overall survival (p = 0.003, p = 0.034, respectively), while in multivariate regression analysis TGF-β1 manifested as an independent predictor of poor outcome. Conclusions: Unraveling the complex roles and significance of TGF-β signaling in urothelial bladder cancer might have important implications for therapy of this disease. Assessment of TGF-β pathway status in patients with urothelial bladder cancer may provide useful prognostic information, and identify patients that could have the most benefit from therapy targeting TGF-β signaling cascade.	bladder
Immunohistochemistry in the workup of bladder biopsies: Frequency, variation and utility of use at an academic center.	"INTRODUCTION: Flat urothelial lesions fall into one of four diagnostic categories including urothelial carcinoma in-situ (CIS). There is morphologic overlap between the categories leading to immunohistochemistry (IHC) utilization in difficult cases. The purpose of this study was to examine the frequency, variation and utility of IHC use in bladder biopsy specimens over a 17 year period. METHODS: A search of ""CD44"", ""p53"", and ""CK20"" keywords was conducted from the pathology files (1/1/2003 to 12/31/2017) on bladder biopsy specimens at our institution. Atypical (AUS), dysplastic (UD) and CIS rates were calculated. RESULTS: A total of 4597 cases were identified. IHC was performed on 345 specimens (7.5%, 345/4597). For cases without IHC (H&E only), the AUS rate was 4.8% (206/4252), UD rate was 9.4% (399/4252), and the CIS rate was 8.4% (359/4252). For IHC cases, the AUS rate was 5.2% (18/345), the UD rate was 8.1% (28/345), and the CIS rate was 11.3% (39/345). There was no statistical difference between the H&E only or IHC rates (p > 0.05). The absolute number IHC orders per year increased until 2011 (60 cases) but drastically declined over the last five years (5 total cases in 2017). The CIS rates have remained relatively constant. CONCLUSION: We found the AUS, UD and CIS rates were similar regardless of IHC use. Our institution was an early adopter of IHC and it quickly fell out of favor. We agree with the ISUP in that IHC has limited clinical utility for flat urothelial lesions and morphology remains the gold standard."	bladder
Time from incident primary cancer until recurrence or second primary cancer: Risk factors and impact in general practice.	OBJECTIVE: Specialised follow-up care after cancer treatment is changing towards increased involvement of general practice. To ensure timely detection of new cancer events, knowledge is warranted on the timing of cancer recurrence (CR) and second primary cancer (SPC), including risk factors for CR. METHODS: This population-based register study included 67,092 patients diagnosed with malignant melanoma, bladder, lung, ovarian, endometrial, colorectal and breast cancer in Denmark in 2008-2016. The time from primary cancer to CR or SPC and risk factors for prolonged time to CR were analysed and stratified on sex and primary cancer type. RESULTS: Cancer recurrence proportions ranged from 6% to 35%. The risk of CR increased profoundly within the first 3 years and then levelled off, except for breast cancer. A total of 3%-6% of patients had SPC, with monotonously increasing cumulative incidence proportions. Besides primary tumour characteristics, lower educational level, living alone and comorbidity were associated with earlier CR. For example, in female malignant melanoma, HRs and 95% confidence intervals were 0.47 (0.37-0.61) for high educational level, 1.40 (1.16-1.68) for living alone and 2.38 (1.53-3.70) for high comorbidity. CONCLUSION: The results may inform stratified risk assessment in decision of frequency, location and duration of post-cancer follow-up care.	bladder
Reduction of Pain during Flexible Cystoscopy: A Systematic Review and Meta-Analysis.	PURPOSE: The BCAN (Bladder Cancer Advocacy Network) Patient Survey Network identified pain during intravesical procedures as a research priority for patients. Although intraurethral lidocaine is the standard of care in this setting, evidence of its use is equivocal. We systematically reviewed studies of interventions to reduce discomfort during cystoscopy and intravesical therapy of bladder cancer. We performed a meta-analysis of interventions using available randomized, controlled trials. MATERIALS AND METHODS: Search terms derived from the key questions were incorporated into the literature search constructed by a research librarian and the English medical literature from 1990 to 2017 was accessed. The initial search yielded 626 potential studies and the final review incorporated 62. We combined 12 trials into a meta-analysis with a random effects model of the efficacy of intraurethral lidocaine vs plain lubricant to reduce pain during flexible cystoscopy as measured on a 10-point visual analogue scale. RESULTS: Data from 12 randomized controlled trials in a total of 1,549 patients were included in the final intraurethral lidocaine meta-analysis. The standardized mean difference between visual analogue scale pain scores in patients who underwent flexible cystoscopy with intraurethral lidocaine and plain lubricant was -0.22 (95% CI -0.39--0.05). Evidence was insufficient to evaluate other interventions to mitigate the discomfort of invasive bladder procedures. CONCLUSIONS: Intraurethral lidocaine provides statistically significant pain reduction in men who undergo flexible cystoscopy, particularly with a longer dwell time. The evidence was insufficient for other tested interventions. A prospective study is needed to further clarify interventions to decrease patient discomfort during cystoscopy and other intravesical procedures in a diverse population.	bladder
Identifying and Codifying Complications after Radical Cystectomy: Comparison of Administrative Diagnostic and Procedure Codes, and Clinical Chart Review.	PURPOSE: To our knowledge the reliability of administrative claims codes to report postoperative radical cystectomy complications has not been examined. We compared complications identified by claims data to those abstracted from clinical chart review following radical cystectomy. METHODS: We manually reviewed the charts of 268 patients treated with radical cystectomy between 2014 and 2016 for 30-day complications and queried administrative complication coding using 805 ICD-9/10 codes. Complications were categorized. Using Cohen κ statistics we assessed agreement between the 2 methods of complication reporting for 1 or more postoperative complications overall, categorical complications and complications stratified by the top quartile length of hospital stay and patients who were readmitted. RESULTS: At least 1 or more complications were recorded in 122 patients (45.5%) through manual chart review and 80 (29.9%) were recorded via claim coding data with a concordance rate of κ=0.16, indicating weak agreement. Concordance was generally weak for categorical complication rates (range 0.05 to 0.36). However, when examining only the top length of stay quartile, 1 or more complications were reported in 32 patients (65%) by the manual chart review and in 12 (25%) via coding data with a concordance rate of κ=-0.2. Agreement was weak, similar to the total cohort. CONCLUSIONS: Manual chart review and claim code identification of complications are not highly concordant even when stratified by patients with an extended length of stay, who are known to have more frequent complications. Researchers and administrators should be aware of these differences and exercise caution when interpreting complication reports.	bladder
HSDL2 Promotes Bladder Cancer Growth In Vitro and In Vivo.	Bladder cancer is a common malignant urinary tumor, and patients with bladder cancer have poor prognosis. Abnormal lipid metabolism in peroxisomes is involved in tumor progression. Hydroxysteroid dehydrogenase-like 2 (HSDL2) localized in peroxisomes regulates fatty acid synthesis. In the present study, we reported that HSDL2 was upregulated in two human bladder cancer cell lines 5637 and T24 compared to normal human urothelial cells. Furthermore, lentiviral-mediated HSDL2 knockdown inhibited the proliferation and colony formation while promoted the apoptosis of human bladder cancer T24 cells in vitro. In nude mice HSDL2 knockdown inhibited the growth of T24 derived xenografts in vivo. In conclusion, our results suggest that HSDL2 plays an oncogenic role in bladder cancer and might serve as a potential target for bladder cancer therapy.	bladder
Life and bladder cancer: protocol for a longitudinal and cross-sectional patient-reported outcomes study of Yorkshire (UK) patients.	INTRODUCTION: Little is known about the impact of bladder cancer (BC) and its treatments on health-related quality of life (HRQL). To date, most work has been small in scale or restricted to subsets of patients. Life and bladder cancer is a cross-sectional and longitudinal study collecting patient-reported outcomes within two distinct cohorts. METHODS AND ANALYSIS: A longitudinal study will collect patient-reported outcomes at 3-monthly intervals from newly diagnosed patients. Eligible cases will be identified by recruiting hospitals and surveyed at baseline, 6, 9 and 12 months postdiagnosis to explore changes in outcomes over time. A separate cross-sectional cohort of patients diagnosed within the last 10 years across Yorkshire will be identified through cancer registration systems and surveyed once to explore longer-term HRQL in BC survivors. A comprehensive patient-reported outcome measure (PROM) has been developed using generic, cancer-specific and BC-specific instruments. The study will provide evidence about how useful these PROMs are in measuring BC patient HRQL. The outcome data will be linked with administrative health data (eg, treatment information from hospital data). ETHICS AND DISSEMINATION: The study has received the following approvals: Yorkshire and the Humber-South Yorkshire Research Ethics Committee (17/YH/0095), Health Research Authority Confidentiality Advisory Group (17/CAG/0054). Results will be made available to patients, funders, NHS Trusts, Clinical Commissioning Groups, Strategic Clinical Networks and other researchers.	bladder
Regulator of G protein signaling 20 promotes proliferation and migration in bladder cancer via NF-κB signaling.	BACKGROUND: Bladder cancer is a complicated disease with high rate of morbidity and mortality, in which proliferation and migration are both well acknowledged as aggressive phenotypes of bladder cancer cells. A better understanding of the mechanisms of tumor proliferation and migration would provide an insight into cancer progression and provide effective therapeutic strategies. METHODS: The expression of RGS20 was detected using qRT-PCR,western blotting and immunohistochemistry. MTT, Colony formation, anchorage-independent growth assay, and transwell assay were used to evaluate the pro-proliferation and pro-migration potential of RGS20 in vitro. Tumor growth was monitored and analyzed in an animal model. Luciferase activity assay, nuclear extract analysis, and multiple blockade of NF-κB were used to evaluate NF-κB signaling activity. RESULTS: It revealed that RGS20 was significantly upregulated in bladder cancer and increased RGS20 expression correlated significantly with worse 5-year overall survival. Ectopic overexpression of RGS20 accelerated the proliferation and migration of bladder cancer cells, whereas knockdown of RGS20 inhibited these effects. Mechanistically, RGS20 could activate NF-κB signaling, which played a crucial role in RGS20's effects on proliferation, migration, and tumorigenicity of bladder cancer cells. CONCLUSION: Our study highlights that RGS20 acted as an oncogene in bladder cancer and a better understanding of RGS20's functions might provide the potential for clinical intervention in this disease.	bladder